Schwartz Ann G, Prysak Geoffrey M, Murphy Valerie, Lonardo Fulvio, Pass Harvey, Schwartz Jan, Brooks Sam
Population Studies and Prevention Program, and Breast Cancer Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Clin Cancer Res. 2005 Oct 15;11(20):7280-7. doi: 10.1158/1078-0432.CCR-05-0498.
A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival.
Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status.
Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors.
This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas.
报道的肺癌易感性和生存率方面的性别差异提示雌激素在决定肺癌风险和预后中起作用。对存档肺组织进行评估，检测核雌激素受体（ER）-α和ER-β的存在情况以及ER状态、受试者特征和生存率之间的关系。
从两项基于人群的病例对照研究中获取214名女性和64名男性的石蜡包埋肺肿瘤样本，以及10名无癌症患者的正常肺尸检样本。通过免疫组织化学法测定核ER-α和ER-β的表达。采用逻辑回归确定与ER阳性相关的因素，采用Cox比例风险模型根据ER状态测量生存差异。
肿瘤组织（94例中0例）和正常肺组织（10例中0例）均未检测到ER-α染色阳性。61%的肿瘤组织样本（278例中的170例；男性为70.3%，女性为58.3%）和20%的正常组织样本（10例中的2例；P = 0.01）检测到核ER-β阳性。在多变量分析中，女性发生ER-β阳性肿瘤的可能性比男性低46%（优势比，0.54；95%置信区间，0.27 - 1.08）。这种关系在腺癌中更强且具有统计学意义（优势比，0.40；95%置信区间，0.18 - 0.89）。与ER-β阴性肿瘤患者相比，ER-β阳性肿瘤的女性患者死亡率有不显著的73%（P = 0.1）升高，而ER-β阳性肿瘤的男性患者死亡率有显著的55%（P = 0.04）降低。
本研究提示肺癌中核ER-β存在性别差异表达，并对男性生存率有影响，尤其是在腺癌中。
